Distribution of the Mediterranean ribbed limpet Patella ferruginea Gmelin, 1791 along the Ligurian coast and implications for conservation actions

Patella ferruginea is a limpet endemic to the Western Mediterranean Sea. It is presently considered the most threatened marine macroinvertebrate in the region and has been included in several international conservation directives. Its populations were widespread throughout the Western Mediterranean in the late Pleistocene period, and remained broadly distributed until the 19th century. Presently this species is confined into small populations in a few restricted areas due to human harvesting for food and baits, construction of coastal infrastructures and the effects of seawater pollution. In particular, the species is reported as presently disappeared from the whole of the Italian continental coast and measures are in progress to reintroduce the species through translocation and reproduction in controlled conditions along the Ligurian coasts of the Northwestern Mediterranean.Recent surveys implemented in the framework of the present work along the Ligurian coasts, to assess the most suitable sites for reintroduction, resulted in the discovery of 32 specimens of this endemic limpet, which previously was thought to have vanished from the area. These findings shed new light on the ability of species to naturally disperse, the relevance of the measures set in place to restore presently rarefied populations and may provide information to aid in the selection and management of sites within the Natura 2000 Ecological network

Efficacy and safety of emapalumab in macrophage activation syndrome

OBJECTIVES: Macrophage activation syndrome (MAS) is a severe, life-threatening complication of systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD). The objective of this study was to confirm the adequacy of an emapalumab dosing regimen in relation to interferon-γ (IFNγ) activity by assessing efficacy and safety. The efficacy outcome was MAS remission by week 8, based on clinical and laboratory criteria. METHODS: We studied emapalumab, a human anti-IFNγ antibody, administered with background glucocorticoids, in a prospective single-arm trial involving patients who had MAS secondary to sJIA or AOSD and had previously failed high-dose glucocorticoids, with or without anakinra and/or ciclosporin. The study foresaw 4-week treatment that could be shortened or prolonged based on investigator's assessment of response. Patients entered a long-term (12 months) follow-up study. RESULTS: Fourteen patients received emapalumab. All patients completed the trial, entered the long-term follow-up and were alive at the end of follow-up. The investigated dosing regimen, based on an initial loading dose followed by maintenance doses, was appropriate, as shown by rapid neutralisation of IFNγ activity, demonstrated by a prompt decrease in serum C-X-C motif chemokine ligand 9 (CXCL9) levels. By week 8, MAS remission was achieved in 13 of the 14 patients at a median time of 25 days. Viral infections and positive viral tests were observed. CONCLUSIONS: Neutralisation of IFNγ with emapalumab was efficacious in inducing remission of MAS secondary to sJIA or AOSD in patients who had failed high-dose glucocorticoids. Screening for viral infections should be performed, particularly for cytomegalovirus. TRIAL REGISTRATION NUMBER: NCT02069899 and NCT03311854

A role for the polyol pathway in the early neuroretinal apoptosis and glial changes induced by diabetes in the rat. Diabetes 52: 506–511

We tested the hypothesis that the apoptosis of inner retina neurons and increased expression of glial fibrillary acidic protein (GFAP) observed in the rat after a short duration of diabetes are mediated by polyol pathway activity. Rats with 10 weeks of streptozotocininduced diabetes and GHb levels of 16 ؎ 2% (mean ؎ SD) showed increased retinal levels of sorbitol and fructose, attenuation of GFAP immunostaining in astrocytes, appearance of prominent GFAP expression in Mü ller glial cells, and a fourfold increase in the number of apoptotic neurons when compared with nondiabetic rats. The cells undergoing apoptosis were immunoreactive for aldose reductase. Sorbinil, an inhibitor of aldose reductase, prevented all abnormalities. Intensive insulin treatment also prevented most abnormalities, despite reducing GHb only to 12 ؎ 1%. Diabetic mice, known to have much lower aldose reductase activity in other tissues when compared with rats, did not accumulate sorbitol and fructose in the retina and were protected from neuronal apoptosis and GFAP changes in the presence of GHb levels of 14 ؎ 2%. This work documents discrete cellular consequences of polyol pathway activity in the retina, and it suggests that activation of the pathway and "retinal neuropathy" require severe hyperglycemia and/or high activity of aldose reductase. These findings have implications for how to evaluate the role of the polyol pathway in diabetic retinopathy